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演題詳細

Oral

幹細胞、ニューロンとグリアの分化 2
Stem Cells, Neuronal and Glial Production/Differentiation 2

開催日 2014/9/12
時間 15:00 - 16:00
会場 Room J(313+314)
Chairperson(s) 榎本 秀樹 / Hideki Enomoto (神戸大学大学院医学研究科 生理学・細胞生物学講座 神経分化・再生分野 / Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, Japan)
小曽戸 陽一 / Yoichi Kosodo (川崎医科大学 解剖学 / Department of Anatomy, Kawasaki Medical School, Japan)

ポリコームドメインの拡大が大脳新皮質神経系前駆細胞のニューロン分化能を制限する
Locus-specific expansion of Polycomb domain determines the temporal repression of the neurogenic genes in neocortical development

  • O2-J-3-4
  • 岸 雄介 / Yusuke Kishi:1 平林 祐介 / Yusuke Hirabayashi:2 Tyssowski Kelsey / Kelsey Tyssowski:2 古関 明彦 / Haruhiko Koseki:3 鈴木 穣 / Yutaka Suzuki:4 後藤 由季子 / Yukiko Gotoh:1 
  • 1:東京大院薬 / Grad Sch Pharma, Univ of Tokyo, Japan 2:東京大院分生研 / IMCB, Univ of Tokyo, Japan 3:理研・IMS-RCAI・免疫器官形成 / RIKEN, IMS-RCAI, Japan 4:東京大院新領域創成科学 / Grad Sch Frontier Sci, Univ of Tokyo, Japan 

The temporally and spatially restricted nature of the differentiation capacity of somatic stem cells in development has been studied extensively in recent years. Epigenetic control of developmental genes, which is heritable through cell divisions, has emerged as a key mechanism defining the differentiation potential of cells. In this fundamental step of embryonic development, Polycomb group complex (PcG) plays a key role in repressing developmental genes through trimethylation of histone H3K27 (H3K27me3). However, how PcG-mediated gene repression is temporally regulated remains largely unknown.
During neocortical development, neural precursor cells (NPCs), the tissue stem cells, which generate various nervous cell types in the neocortex, undergo gradual fate restriction. In the early stages of neocortical development, NPCs have the potential to generate various types of neurons and glial cells. In contrast, NPCs in the late stages mainly generate glial cells. Since controlling the order of cells to be produced is thought to be important for development of a functional brain, revealing the fate restriction mechanism of NPC is crucial for understanding neocortical development. Previously, we have shown that PcG proteins mediate the neurogenic-to-gliogenic switch of NPC fate, in part through suppressing the proneural gene Neurogenin1.
In the present study, we performed ChIP-seq analysis with anti-H3K27me3 antibody and gene expression analysis in NPCs at various stages of the neocortical development. We found that genes, which become repressed in the astrogliogenic phase, gain H3K27me3 mark at their proximal promoter regions and transcription start sites (TSSs) during development. Surprisingly, these genes already harbor H3K27me3 mark at their distal promoter regions (1-4 kbp upstream of TSSs) in the neurogenic phase, even they are expressed. These results suggest that expansion of PcG occupancy from the distal to proximal promoter region triggers gene repression in the developing neocortical NPCs. We are currently investigating the potential role of chromatin proteins in regulating the expansion of H3K27me3 domains.

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